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Background The high rates of local relapse observed in prostate cancer patients with conventional radiation techniques have stimulated research to develop high precision radiation to decrease the risks of local recurrence. The three dimensional conformal approach applies sophisticated computer-driven techniques, programmed to deliver the prescribed radiation dose to the entire target volume, while conforming to the anatomical boundaries of the tumor in its entire three-dimensional configuration. This study is a prospective phase I dose escalation study conducted to determine the maximally tolerated radiation dose in men treated with 3D conformal RT for localized prostate cancer. This is a preliminary report of toxicity at level III (79.2 Gy) on 3DOG/RTOG 9406.

Materials and
Methods

Patients were registered according to three risk groups:
Group 1(G1) clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle (SV) invasion of <15%;
Group 2 (G2) T1,2 disease with risk of SV invasion >=15%;
Group 3(G3) clinical local extension of tumor beyond the prostate capsule (T3).

In order to reduce the rectal dose on level III, the minimum PTV dose was limited to 73.8 Gy whereas the minimum GTV dose was 79.2 Gy in 44 fractions.

G1 patients, the PTV margins were 5-10 mm around the prostate and

G2 patients, the same margins were applied to the prostate and SV. After 55.8 Gy the PTV was reduced in G2 patients to 5-10 mm around the prostate only.

This report describes the acute and late toxicity encountered in G1 and 2 patients treated at dose level III (79.2 Gy).

Results

173 patients were accrued to level III dose of 79.2 cGy on this study.

168 patients are available for analysis of toxicity.

No patients experienced grade 3 or greater acute toxicity.

The acute toxicity rate was comparable to that reported for previous lower dose levels (68.4 Gy and 73.8 Gy) and consisted of minor bladder and bowel irritation. With the median follow-up of 3.0 years (range 0.4-3.9), a total of 3 (1.8%) patients experienced grade 3 late toxicity,

The observed rate of grade 3+ late effects for group I (2 cases) is significantly lower (p=0.0005) than the 15.8 cases that would have been expected from RTOG 7506 and 7706 in the same interval.

The observed rate for group 2 (1 case) is significantly lower (p=0.0024) than the 11.1 cases that were expected.

Author's Conclusions Based on excellent tolerance of 3D conformal RT for stage T1,2 prostate cancer, further biological dose escalation has been pursued to levels IV and V, 74 Gy and 78 Gy respectively, at 2 Gy per day, in an attempt to reduce the total treatment duration. RTOG is planning to evaluate whether this treatment approach improves efficacy.

Clinical/Scientific Implications 3D-conformal RT has been developed, in part, to address the issue of tissue toxicity in the setting of dose escalation. This study demonstrates the ability of the 3D approach to reduce rectal and bladder toxicities. This approach permits an increase in the tumor dose to levels beyond those feasible with conventional two-dimensional radiation therapy, with a concomitant decrease in the risk of normal tissue complications. We await the studies that evaluate the impact on survival.